Lactoferrin causes IgA and IgG2b isotype switching through betaglycan binding and activation of canonical TGF-β signaling

Y. S. Jang, G. Y. Seo, J. M. Lee, H. Y. Seo, H. J. Han, S. J. Kim, B. R. Jin, H. J. Kim, S. R. Park, Kijong Rhee, W. S. Kim, P. H. Kim

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Lactoferrin (LF), a pleiotropic iron-binding glycoprotein, is known to modulate the humoral immune response. However, its exact role in Ig synthesis has yet to be elucidated. In this study, we investigated the effect of LF on Ig production by mouse B cells and its underlying mechanisms. LF, like transforming growth factor (TGF)-β1, stimulated B cells to produce IgA and IgG2b, while downregulating other isotypes. Using limiting dilution analysis, LF was shown to increase the frequency of IgA-secreting B-cell clones. This was paralleled by an increase in Ig germ-line α (GLα) transcripts, indicating that LF plays a role as an IgA switch factor. Interestingly, LF directly interacted with betaglycan (TGF-β receptor III, TβRIII) and in turn induced phosphorylation of TβRI and Smad3 through formation of the TβRIII/TβRII/TβRI complex, leading to IgA isotype switching. Peroral administration of LF increased intestinal/serum IgA production as well as number of IgA plasma cells in lamina propria. Finally, we found that LF has an adjuvant activity when nontoxigenic Salmonella typhimurium was inoculated perorally, conferring protection against intragastrical infection of toxigenic S. typhimurium. These results suggest that LF has an important effect on the mucosal/systemic IgA response and can contribute to protection against intestinal pathogens.

Original languageEnglish
Pages (from-to)906-917
Number of pages12
JournalMucosal Immunology
Volume8
Issue number4
DOIs
Publication statusPublished - 2015 Jul 25

Fingerprint

Immunoglobulin Class Switching
Lactoferrin
Transforming Growth Factors
Immunoglobulin A
B-Lymphocytes
Salmonella typhimurium
betaglycan
Growth Factor Receptors
Humoral Immunity
Plasma Cells
Germ Cells
Glycoproteins
Mucous Membrane
Down-Regulation
Iron
Clone Cells
Phosphorylation

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Jang, Y. S. ; Seo, G. Y. ; Lee, J. M. ; Seo, H. Y. ; Han, H. J. ; Kim, S. J. ; Jin, B. R. ; Kim, H. J. ; Park, S. R. ; Rhee, Kijong ; Kim, W. S. ; Kim, P. H. / Lactoferrin causes IgA and IgG2b isotype switching through betaglycan binding and activation of canonical TGF-β signaling. In: Mucosal Immunology. 2015 ; Vol. 8, No. 4. pp. 906-917.
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title = "Lactoferrin causes IgA and IgG2b isotype switching through betaglycan binding and activation of canonical TGF-β signaling",
abstract = "Lactoferrin (LF), a pleiotropic iron-binding glycoprotein, is known to modulate the humoral immune response. However, its exact role in Ig synthesis has yet to be elucidated. In this study, we investigated the effect of LF on Ig production by mouse B cells and its underlying mechanisms. LF, like transforming growth factor (TGF)-β1, stimulated B cells to produce IgA and IgG2b, while downregulating other isotypes. Using limiting dilution analysis, LF was shown to increase the frequency of IgA-secreting B-cell clones. This was paralleled by an increase in Ig germ-line α (GLα) transcripts, indicating that LF plays a role as an IgA switch factor. Interestingly, LF directly interacted with betaglycan (TGF-β receptor III, TβRIII) and in turn induced phosphorylation of TβRI and Smad3 through formation of the TβRIII/TβRII/TβRI complex, leading to IgA isotype switching. Peroral administration of LF increased intestinal/serum IgA production as well as number of IgA plasma cells in lamina propria. Finally, we found that LF has an adjuvant activity when nontoxigenic Salmonella typhimurium was inoculated perorally, conferring protection against intragastrical infection of toxigenic S. typhimurium. These results suggest that LF has an important effect on the mucosal/systemic IgA response and can contribute to protection against intestinal pathogens.",
author = "Jang, {Y. S.} and Seo, {G. Y.} and Lee, {J. M.} and Seo, {H. Y.} and Han, {H. J.} and Kim, {S. J.} and Jin, {B. R.} and Kim, {H. J.} and Park, {S. R.} and Kijong Rhee and Kim, {W. S.} and Kim, {P. H.}",
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Jang, YS, Seo, GY, Lee, JM, Seo, HY, Han, HJ, Kim, SJ, Jin, BR, Kim, HJ, Park, SR, Rhee, K, Kim, WS & Kim, PH 2015, 'Lactoferrin causes IgA and IgG2b isotype switching through betaglycan binding and activation of canonical TGF-β signaling', Mucosal Immunology, vol. 8, no. 4, pp. 906-917. https://doi.org/10.1038/mi.2014.121

Lactoferrin causes IgA and IgG2b isotype switching through betaglycan binding and activation of canonical TGF-β signaling. / Jang, Y. S.; Seo, G. Y.; Lee, J. M.; Seo, H. Y.; Han, H. J.; Kim, S. J.; Jin, B. R.; Kim, H. J.; Park, S. R.; Rhee, Kijong; Kim, W. S.; Kim, P. H.

In: Mucosal Immunology, Vol. 8, No. 4, 25.07.2015, p. 906-917.

Research output: Contribution to journalArticle

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T1 - Lactoferrin causes IgA and IgG2b isotype switching through betaglycan binding and activation of canonical TGF-β signaling

AU - Jang, Y. S.

AU - Seo, G. Y.

AU - Lee, J. M.

AU - Seo, H. Y.

AU - Han, H. J.

AU - Kim, S. J.

AU - Jin, B. R.

AU - Kim, H. J.

AU - Park, S. R.

AU - Rhee, Kijong

AU - Kim, W. S.

AU - Kim, P. H.

PY - 2015/7/25

Y1 - 2015/7/25

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